Tumor cells can be induced to differentiate and to revert to a normal phenotype. Leukemic cells can be effectively induced to differentiate into macrophages or granulocytes or heme producing cells by radiation and a large number of antitumor agents. Active test is being organized to induce malignant cell differentiation as a therapeutic approach. Several reasons suggest that commonly used therapeutic radiation scheme is a potent method to induce tumor cell differentiation. Unlike cell killing action, the dose required for differentiation is probably lower but may require repeated or prolonged treatment. In addition, differentiation capacity in fractioned radiation treatment is not reduced and the effect of radiation can act additively to other inducers. Differentiation is an under- estimated benefit in radiotherapy. However, clinical radiation treatment procedures in terms of total dose, fractionation, and dose-rate may actually provide greater stimulating effect to tumor cell differentiation than single fraction or other agents inducing cell differentiation. We propose to use colon carcinoma cell lines, HT-29 and SW480, cultured as monolayers and spheroids as models to evaluate the effect of ionizing radiation. Furthermore, we propose to determine the mechanisms underlying the radiation induced alteration on gene expression and/or the structure and function of cell membrane.